Digoxin and Quinidine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Digoxin
Quinidine
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased digoxin exposure
Interaction Deep Dive
Coadministration of digoxin and quiNIDine (P-gp inhibitor) may increase digoxin exposure. Measure digoxin exposure before initiating concomitant drugs. Reduce digoxin concentrations by decreasing dose by approximately 30-50% or by modifying the dosing frequency and continue monitoring1243. Also, monitor potential signs and symptoms of clinical toxicity is necessary when initiating, adjusting, or discontinuing quiNIDine 43.
Why it happens (mechanism)
Inhibition of P-gp mediated efflux transport of digoxin
Literature reports
5 reports — tap to read
a) In pharmacokinetic studies, the concomitant administration of quiNIDine and digoxin increased serum digoxin concentrations by 100% 12. Concomitant administration of quiNIDine and IV digoxin increased digoxin AUC by 54% to 83% 43.
b) The effect of digoxin on the pharmacokinetics of quiNIDine was studied in 6 healthy volunteers. Alterations were found in the pharmacokinetics of quiNIDine, including significantly reduced elimination and increased half-life. The AUC of quiNIDine was elevated, but not significantly. Digoxin had a significantly increased AUC resulting from reduced renal and total digoxin clearance 6.
c) Serum digoxin levels were observed in 27 patients on steady-state doses of digoxin, who were not taking any other antiarrhythmic drugs before or during quiNIDine therapy 7. In 25 patients, the serum digoxin level rose significantly during quiNIDine therapy from a mean level of 1.4 nanogram/mL (ng/mL); 1.79 nanomol/L to 3.2 ng/mL (4.1 nanomol/L), in spite of a reduction in the mean dose of digoxin from 0.31 mg to 0.25 mg. Anorexia, nausea, and vomiting developed in 16 patients on combination therapy, and disappeared in 10 patients when the digoxin dose was lowered or held. Four patients with prior ventricular arrhythmias experienced a worsened arrhythmia within 5 days after quiNIDine was initiated. Of 13 patients without prior ventricular premature beats, 3 developed this symptom in the same time period. One of those patients manifested ventricular fibrillation, one had asystole, and there was one sudden death. Similar but lesser effects have also been reported with digitoxin 8.
d) Alteration in renal clearance may be due to decreased renal-tubular secretion of digoxin 95. An average 42% decrease in biliary clearance of digoxin when co-treated with quiNIDine was reported 10. The effect of quiNIDine digoxin t(1/2) ranges from no significant change 1112 to a significant increase 1314.
e) The literature is conflicting regarding the clinical significance of the increase in serum digoxin levels. Although digitalis toxicity has been reported, several studies have reported a decrease in myocardial performance in the presence of elevated serum digoxin concentration during quiNIDine therapy 1516175. Research suggests that the decrease in tissue binding may decrease the efficacy of digoxin despite increased levels, making dosage adjustments of digoxin unnecessary during combined treatment 18. Routine downward adjustments of the digoxin dose by 50% have been recommended by others whenever quiNIDine is added to the regimen 19.
Common questions
Can I take Digoxin and Quinidine together?
Increased digoxin exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Digoxin and Quinidine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Digoxin or Quinidine need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (19)
- Product Information: LANOXIN(R) oral tablets, digoxin oral tablets. Concordia Pharmaceuticals Inc (per FDA), Kansas City, MO, 2019. DailyMed
- Product Information: DIGOXIN oral tablets, digoxin oral tablets. Aurobindo Pharma USA, Inc. (per Dailymed), East Windsor, NJ, May. DailyMed
- Product Information: DIGOXIN intravenous injection, digoxin intravenous injection. Hikma Pharmaceuticals USA Inc. (per Dailymed), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: LANOXIN® intravenous, intramuscular injection, digoxin intravenous, intramuscular injection. Covis Pharma (per FDA), King of Prussia, PA, 2025. DailyMed
- Rodin SM & Johnson BF: Pharmacokinetic interactions with digoxin. Clin Pharmacokinet 1988; 15:227-244. PubMed
- Rameis H: Quinidine-digoxin interaction: are the pharmacokinetics of both drugs altered?. Int J Clin Pharmacol Ther Toxicol 1985; 23:145-153.
- Leahey EB Jr, Reiffel JA, Drusin RE, et al: Interaction between quinidine and digoxin. JAMA 1978; 240:533-534.
- Kuhlmann J, Dohrmann M, & Marcin S: Effects of quinidine on pharmacokinetics and pharmacodynamics of digitoxin achieving steady-state conditions. Clin Pharmacol Ther 1986; 39:288-294. PubMed
- Fichtl B & Doering W: The quinidine-digoxin interaction in perspective. Clin Pharmacokinet 1983; 8:137-154. PubMed
- Hedman A, Angelin B, Arvidsson A, et al: Interactions in the renal and biliary elimination of digoxin: stereoselective difference between quinine and quinidine. Clin Pharmacol Ther 1990; 47:20-26. PubMed
- Hager WD, Fenster P, Mayersohn M, et al: Digoxin-quinidine interaction. Pharmacokinetic evaluation. N Engl J Med 1979; 300:1238-1241. DOI
- Doering W, Fichtl B, Hermann M, et al: Quinidine-digoxin interaction: evidence for involvement of an extrarenal mechanism. Eur J Clin Pharmacol 1982; 21:281-285. PubMed
- Schenck-Gustafsson K & Dahlqvist R: Pharmacokinetics of digoxin in patients subjected to the quinidine-digoxin interaction. Br J Clin Pharmacol 1981; 11:181-186. DOI
- Ochs HR, Bodem G, & Greenblatt DJ: Impairment of digoxin clearance by coadministration of quinidine. J Clin Pharmacol 1981; 21:396-400. PubMed
- Steiness E, Waldorff S, Hansen PB, et al: Reduction of digoxin-induced inotropism during quinidine administration. Clin Pharmacol Ther 1980; 27:791-795. DOI
- Hirsh PD, Weiner HJ, & North RL: Further insights into digoxin-quinidine interaction: Lack of correlation between serum digoxin concentration and inotropic state of the heart. Am J Cardiol 1980; 46:863-868. PubMed
- Bussey HI: Update on the influence of quinidine and other agents in digitalis glycosides. Am Heart J 1984; 107:143-146.
- Doherty JE, Straub KD, Murphy ML, et al: Digoxin-quinidine interaction. Changes in canine tissue concentration from steady state with quinidine. Am J Cardiol 1980; 45:1196-1200. DOI
- Bigger JT Jr: The quinidine-digoxin interaction. Mod Concepts Cardiovasc Dis 1982; 51:73-78.
Keep reading about Digoxin
Keep reading about Quinidine
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